An Opioid That's One Thousand Times More Potent Than Morphine Is Approved at Height of Opioid Addiction Crisis

An estimated 202,600 Americans died from opioid overdoses between 2002 and 2015,1 and drug overdoses are now the leading cause of death among Americans under the age of 50.2

Despite all the public warnings and national efforts to rein in this lethal trend, overdose cases admitted into emergency rooms still increased by more than 30 percent across the U.S. between July 2016 and September 2017,3 and provisional data suggests the death toll from opioids was around 49,000 in 2017,4 up from 42,250 in 2016.5

Aside from the staggering death toll, addiction to narcotic pain relievers also places an enormous economic burden on society, costing the U.S. an estimated $504 billion each year (2.8 percent of gross domestic product), according to a November 2017 White House report.6,7

Food and Drug Administration Approves Most Potent Opioid Yet

Despite the fact we're not seeing any evidence of reversal of this burgeoning epidemic, the U.S. Food and Drug Administration (FDA) has approved the most potent synthetic opioid painkiller to date, called Dsuvia (sufentanil),8,9 — a drug 1,000 times stronger than morphine, 50 times more potent than heroin and 10 times stronger than the synthetic opioid fentanyl.10,11

FDA commissioner Scott Gottlieb commented on the decision in a November 2, 2018, written statement:12

"There are very tight restrictions being placed on the distribution and use of this product. We've learned much from the harmful impact that other oral opioid products can have in the context of the opioid crisis. We've applied those hard lessons as part of the steps we're taking to address safety concerns for Dsuvia."

Dsuvia Approval Is a Reckless Move, Critics Say

Critics, however, say Dsuvia is completely unnecessary, and that its potency renders it a target for misuse and/or illegal sale13 — two key problems that currently plague most narcotic pain relievers.

Sen. Ed Markey, (D-MA), urged the FDA to deny approval for Dsuvia in October, saying,14 "An opioid that is a thousand times more powerful than morphine is a thousand times more likely to be abused, and a thousand times more likely to kill." Drug prevention and treatment experts in New Jersey agree.

Angelo Valente, executive director of the Partnership for a Drug-Free New Jersey, told a local news station,15 "There's no question that we are extremely concerned that a drug of that kind of magnitude can wind up in the wrong hands … we don't understand why this particular type of drug is even necessary."

Don Parker, president of the Carrier Clinic,16 a New Jersey-based addiction treatment facility, also predicts trouble. "We think there will be a frenzy for this because it promises a much stronger high," he says.17

He also notes that since Dsuvia is a synthetic opioid, it won't be long before producers of illicit drugs have deconstructed it and are able to reproduce it, and due to its extreme potency and therefore tiny size, tablets can be easily transported and distributed.

Indeed, we've already seen this with fentanyl, which is flooding into the U.S. via regular mail. A single standard envelope can hold enough fentanyl to get 50,000 people high, and synthetic opioids alone killed 27,000 Americans in 2017, up from 5,500 in 2014.18 (The total death toll for opioids was around 49,000 according to provisional data for 2017,19 up from 42,250 in 2016.20)

The potency of the drug also makes it resistant to naloxone, used to reverse opioid overdoses. Several doses typically need to be administered in case of a fentanyl overdose, and many still die.21 A Dsuvia overdose, being 100 times more potent than fentanyl, may prove impossible to reverse.

"It is certain that Dsuvia will worsen the opioid epidemic and kill people needlessly. It will be taken by medical personnel and others for whom it has not been prescribed. And many of those will overdose and die."

What's so Special About Dsuvia?

The maker of Dsuvia, AcelRx Pharmaceuticals, dismisses such critique, saying the drug is for acute pain use in a medical setting only, and will not be dispensed through pharmacies. For this reason, "It will not contribute to the large outpatient opioid crisis," Dr. Pamela Palmer, cofounder of AcelRx, says.23

The drug is expected to be available in hospitals by the beginning of next year, and annual sales are projected to hit $1.1 billion. As reported by NPR:24

"While sufentanil is potent, the dose in Dsuvia is premeasured and small: 30 micrograms, or millionths of a gram. And Palmer says the product fills a unique need — health care providers put it under patients' tongues, rather than injecting it or giving them a pill to swallow, which, she says, can take too long to offer relief …

She envisions providers using the tablet when finding a vein is difficult and time-sensitive — in emergency room patients who are morbidly obese, for instance … Palmer also says the Department of Defense helped fund the company's research because Dsuvia could potentially be used on the battlefield instead of morphine.

Dr. Sidney Wolfe, senior adviser to Public Citizen's Health Research Group, dismisses Palmer's claim that Dsuvia meets a crucial need … 'It is not unique at all,' Wolfe says, adding that the drug wasn't adequately tested in emergency settings, and that in tests, pain relief with Dsuvia was slow.

In two of the company's studies, Dsuvia patients only felt 'meaningful' pain relief at 54 minutes and 78 minutes."

Strong Opponents Were Excluded From FDA Vote

Critics also note it appears the FDA excluded people who may have raised strong objections, including the chairman of the FDA's Anesthetic and Analgesic Drug Products Advisory Committee, Dr. Raeford Brown, an anesthesiologist at the University of Kentucky.

Brown had informed the FDA about a scheduling conflict months prior to the October 12 hearing on Dsuvia, yet the agency decided to hold the meeting anyway, without him. Brown told NPR,25 "I have strong feelings about the opioid crisis … My forthright nature may have played a role in their decision about how the agency was going to manage this advisory committee."

The Drug Safety and Risk Management Advisory Committee also did not attend the discussions. According to an FDA spokesperson, the drug safety committee was unable to attend due to a scheduling conflict, but according to Brown, "That's not the full story." In a statement, Brown expressed his dismay:26

"I am very disappointed with the decision of the agency to approve Dsuvia. This action is inconsistent with the charter of the agency.

As I discussed with representatives of the agency today, neither the lack of efficacy data, nor the sponsor's response to safety concerns, have been answered. Clearly the issue of the safety of the public is not important to the commissioner, despite his attempts to obfuscate and misdirect."

Nonopioid Pain Relievers Work Just as Well as Opioids for Acute Pain

In the end, time will tell whether Dsuvia truly serves an important niche need, and whether it will end up being grossly misused like most other opioids. Historically, it doesn't look promising. It's also worth noting that recent research has again concluded that opioid-free options often work just as well as narcotic pain relievers for acute pain.

Granted, Dsuvia is extraordinarily potent, but according to the company's own studies, it can take anywhere from 54 to 78 minutes for the drug to provide "meaningful" pain relief.27

A recent study28 published in JAMA evaluated the effects of four different combinations of pain relievers — three with different opioids and one opioid-free option composed of ibuprofen (i.e., Advil) and acetaminophen (i.e., Tylenol) — on people with moderate to severe pain in an extremity due to bone fractures, shoulder dislocation and other injuries.

The patients had an average pain score of 8.7 (on a scale of zero to 10) when they arrived. Two hours later, after receiving one of the pain relief combinations, their pain levels decreased similarly, regardless of which drug-combo they received.

Speaking to Vox, the study's lead author, Dr. Andrew Chang of the department of emergency medicine at Albany Medical College, Albany, New York, said,29 "Some (not all) physicians reflexively think fractures require opioids, but this study lends evidence that opioids are not always necessary even in the presence of fractures."

OxyContin Maker Profits From Patented Opioid Addiction Treatment

As discussed in several previous articles, the massive increase in opioid sales and subsequent addiction rates have been traced back to an orchestrated marketing scheme aimed at misinforming doctors about the drug's addictive potential.

Purdue Pharma, owned by the Sackler family, was one of the most successful in this regard, driving sales of OxyContin up from $48 million in 1996 to $1.5 billion in 2002. Purdue's sales representatives were extensively coached on how to downplay the drug's addictive potential, claiming addiction was occurring in less than 1 percent of patients being treated for pain.

Studies now show addiction actually affects about 26 percent of those using opioids for chronic noncancer pain, and 1 in 550 patients on opioid therapy dies from opioid-related causes within 2.5 years of their first prescription.30

Purdue ended up being fined $634 million in 2007 for misbranding "with intent to defraud and mislead the public,"31 but the Sackler family has not given up on profiting from the "disease" they helped manufacture. Quite the contrary.

In January 2018, Dr. Richard Sackler — who, according to Esquire journalist Christopher Glazek,32 was deeply involved in the marketing of OxyContin as head of the company's research and development, sales and marketing divisions — was awarded a patent for a new, faster-dissolving form of buprenorphine, a mild opioid drug used in the treatment of opioid addiction. As noted by STAT News:33

"… Sackler is listed as one of six inventors on the patent… Critics told the [Financial Times] that they were disturbed that the patent could enable Sackler to benefit financially from the addiction crisis that his family's company is accused of fueling."

Sackler Family Has Also Been Secretly Profiting From Generic Opioids for Over a Decade

But that's not all. The Sacklers have already profited from addiction in more ways than one for over a decade. As reported by Financial Times34 and the New York Post,35 the Sackler family also secretly owns Rhodes Pharma, "one of the biggest producers of generic opioids, which had never before been linked to the family."

What's more, this company was launched just four months after Purdue Pharma's guilty plea back in 2007. When combined, Purdue Pharma and Rhodes Pharma account for about 6 percent of the total opioid market in the U.S.

So, "not only did the Sacklers fail to scale back its marketing of OxyContin after the plea, they further cashed in on the pill crisis — by launching the second firm and selling more of the drug under a different name," the New York Post writes, adding:

"Rhodes [Pharma] was set up as a 'landing pad' in case the underfire drugmaker needed a clean start amid the 2007 criminal charges, a former senior manager at Purdue told the paper.

Together, both firms accounted for 14.4 million opioid prescriptions in 2016. Rhodes Pharma also makes other highly addictive opiates such as morphine, oxycodone and hydromorphone, according to the FDA."

Little Is Known About How to Safely Wean Off Opioids When You're in Chronic Pain

Despite years of growing opioid abuse, there's very little research on how to effectively wean off these drugs when you have chronic pain.36 One scientific review,37 which included 67 studies on tapering opioids for pain patients found only three of the studies to be of high quality; 13 were found to be of "fair" quality, while the rest were weak.

Dr. Stefan Kertesz, an addiction expert at the University of Alabama at Birmingham School of Medicine, told Scientific American38 that "Forced tapers can destabilize patients," and may trigger distress and suicide.

While scant, the available evidence does suggest tapering off the drugs improves both pain and quality of life. In one pilot study39 51 of 68 chronic pain patients successfully completed the four-month program, cutting their opioid dosages nearly in half — without increasing their pain. One of the keys to success was a very slow and gradual reduction in the dose during the first month.

Another study40 evaluating the success rate of Toronto General Hospital's Transitional Pain Program found nearly half of those who had not used opioids prior to surgery successfully weaned themselves off the drugs. Among those who had already used opioids prior to surgery, 1 in 4 was successful. As reported by Science Daily:41

"'The assumption is that all patients after surgery are fine with their opioid use, but we have found that in a high-risk segment of patients, that is not the case,' says Dr. Hance Clarke, director of the Transitional Pain Service at [Toronto General Hospital].

'We need better ways of identifying these patients, and then helping those who are having difficulty in reducing or eliminating their opioid use. Otherwise, we run the risk of de-escalating patients too fast and having them look elsewhere for opioids or other drugs if we don't guide them' …

One of the strongest predictors in the study of remaining on opioids long-term after hospital discharge is the dose upon discharge: the higher the dose, the more likely the patient will remain on opioids long-term.

For patients who were on opioids before surgery, emotional distress factors such as anxiety or depression, and pain catastrophizing — excessive pain-related worry, along with an inability to deflect thoughts from pain — were important factors in how well these patients could wean off opioids."

Guidance for Opioid Weaning

Guidance on opioid tapering published in the March/April issue of the Canadian Pharmacists Journal includes the following highlights:42

• Adult patients with chronic noncancer pain who are on a 90-milligram (mg) morphine equivalent dose daily or greater should consider opioid tapering to the lowest effective dose and discontinue use if possible.

• Gradually reduce 5 to 10 percent of the morphine-equivalent dose every two to four weeks, with frequent follow-up. If on an immediate-release opioid, switch to an extended-release version on a fixed schedule

• Other reasons to consider tapering include lack of improvement in pain and/or function, nonadherence to the treatment plan, signs of addiction, serious opioid-related adverse effects or patient request

• Prescribers are urged to collaborate with pharmacists to support and monitor patients during opioid tapering

• A multidisciplinary approach is associated with success in weaning patients off opioids

• Benefits of tapering include relief of withdrawal symptoms (e.g., pain, sweating or anxiety), reduction in opioid adverse effects and improvements in overall function and quality of life

The Guideline urges physicians to discuss tapering with their patients, and to "prepare them by optimizing nonopioid therapy as appropriate for their pain and comorbidities." This includes the use of acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentinoids43 and cannabinoids, just to name a few.

In the end, considering the steep risks involved,44 the less you expose yourself to opioids, the better. Opioid addiction is very serious, and can occur much faster than you might suspect.

So, when at all possible, exhaust other options before resorting for a narcotic pain reliever, and make every effort to get off it as soon as possible. For a list of suggestions for how to relieve pain without resorting to opioids, see "Do We Really Need Opioids for Pain?"